反应详情

温度

65 °C

A mixture of N′-benzyl-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole-5-carbohydrazide (40 mg, 0.11 mmol) and nicotinimidamide hydrochloride (33 mg, 0.21 mmol) in 2N NaOH ethanol solution (1.1 mL, 0.21 mmol) was heated to 65° C. for 30 min. The mixture was cooled to RT and concentrated under reduced pressure. The crude mixture was taken up in NMP (0.5 mL) and heated to 140° C. for 2 h. The mixture was cooled to RT and partitioned between H2O (0.5 mL) and EtOAc (0.5 mL). The aqueous layer was extracted with EtOAc (3×0.5 mL). The combined organic layers were washed with H2O (3×0.5 mL) and brine (0.5 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude oil was purified by reverse-phase HPLC to provide the TFA salt as a white solid (1.8 mg, 3%): 1H NMR (600 MHz, CDCl3) δ ppm 8.93 (s, 1H), 8.79 (d, J=4.8 Hz, 1H), 8.29 (d, J=8.1 Hz, 2H), 8.08 (d, J=8.0 Hz, 1H), 7.52 (app. dd, J=7.5 Hz, 5.5 Hz, 1H), 7.37-7.30 (m, 5H), 7.20 (d, J=7.3 Hz, 2H), 5.62 (s, 2H); MS (ES+) C23H15F3N6O2 requires: 464. found: 465 [M+H]+.

1. temperatureThe mixture was cooled to RT
2. concentrationconcentrated under reduced pressure
3. temperatureheated to 140° C. for 2 h
4. temperatureThe mixture was cooled to RT
5. custompartitioned between H2O (0.5 mL) and EtOAc (0.5 mL)
6. extractionThe aqueous layer was extracted with EtOAc (3×0.5 mL)
7. washThe combined organic layers were washed with H2O (3×0.5 mL) and brine (0.5 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude oil was purified by reverse-phase HPLC